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REDOX IMAGING OF THE p53-DEPENDENT MITOCHONDRIAL REDOX STATE IN COLON CANCER EX VIVO

Journal of Innovative Optical Health Sciences 2013年第3期6卷 1-10页

作者： HE N.XU MIN FENG LILY MOON NATHAN DOLLOFF WAFIKEL-DEIRY LIN Z.LI Department of Radiology University of Pennsylvania PhiladelphiaPAUSA Britton Chance Laboratory of Redox Imaging Johnson Research Foundation Department of Biochemistry and Biophysics Perelman School of Medicine University of Pennsylvania PhiladelphiaPAUSA Department of Medicine Penn State Hershey Medical Center and Penn State College of MedicineHersheyPAUSA Hematology/Oncology Penn State Hershey Medical Center HersheyPAUSA Abramson Cancer Center University of Pennsylvania PhiladelphiaPAUSA Institute of Translational Medicine and Therapeutics University of Pennsylvania PhiladelphiaPAUSA

The mitochondrial redox state and its heterogeneity of colon cancer at tissue level have not been previously *** has how p53 regulates mitochondial respi ration been measured at(deep)tissue level,presumably due to the unavailability of the technology that has sufficient spatial resolution and tissue penetration *** prior work demonstrated that the mito-chondrial redox state and its intnatumor heterogeneity is associated with cancer aggressiveness in human melanoma and breast cancer in mouse models,with the more metastatic tumons exhi-bit ing localized negions of more oxidized redox *** the Chance redox scanner with an in-plane spatial resolution of 200 pm,we imaged the mitochondrial redox state of the wild-type p53 colon tumors(HCT116 p53 ut)and the p5-deleted colon tumors(HCT116 p53-/-)by cllcting the fuorescence si gnals of nicotinamide adenine dimucleotide(NA DH)and oxidized flavoproteins [Fp,including favin adenine dinucleotide(FAD)]from the mouse xenogmafts snap frozen at low *** results show that:(1)both tumor lines have significant degree of intratumor heterogeneity of the redox state,typically exhibiting a distinct bi modal distribution that either correlates with the spatial core-rim pattern or the“hot/oold”oxida tion-roduction patches;.(2)the p531-group is significantly more beterogencous in the mitochondrial redox state and has a more oxidized turmor core compared to the p53 wt group when the tunor sizes of the two groups are matched;(3)the tumor size dependence of the redox indices(such as Fp and Fp redox ratio)is significant in the p531-group with the larger ones being more oxidized and more hetero-geneous in their redox state,particularly more oxidized in the tumor central regions;(4)the H&E staining images of tumor soctions grossly correlate with the redox *** present work is the first to reveal at the submillimeter scale the intratumor heterogeneity pattem of the mitochon-drial redox state in colon cancer and

关键词： NADH favoprotein intratumor heterogeneity HCT116 p53 null necrotic

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Evolving concepts in bone infection: redefining “biofilm”,“acute vs. chronic osteomyelitis”, “the immune proteome” and “local antibiotic therapy”

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Bone Research 2019年第3期7卷 225-242页

作者： Elysia A. Masters Ryan P. Trombetta Karen L. de Mesy Bentley Brendan F Boyce Ann Lindley Gill Steven R. Gill Kohei Nishitani Masahiro Ishikawa Yugo Morita Hiromu Ito Sheila N. Bello-Irizarry Mark Ninomiya James D. Brodell Jr. Charles C. Lee Stephanie P. Hao Irvin Oh Chao Xie Hani A. Awad John L. Daiss John R. Owen Stephen L. Kates Edward M. Schwarz Gowrishankar Muthukrishnan Center for Musculoskeletal Research University of Rochester Medical Center Rochester NY USA Department of Biomedical Engineering University of Rochester Medical Center Rochester NY USA Department of Pathology and Laboratory Medicine University of Rochester Medical Center Rochester NY USA Department of Orthopaedics University of Rochester Medical Center Rochester NY USA Department of Microbiology & Immunology University of Rochester Medical Center Rochester NY USA Department of Orthopaedic Surgery Kyoto University Kyoto Japan Department of Orthopaedic Surgery Virginia Commonwealth University Medical Center Richmond VA USA

Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus aureus is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity,mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network(OLCN) of cortical bone. In contrast, *** intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome against S. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies(MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure.

关键词： disease caused by soft tissue necrotic tissuel

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Evaluation of necrosis avidity of radioiodinated 5-hydroxytryptophan and its potential applications in myocardial infarction imaging

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Chinese Chemical Letters 2019年第1期30卷 83-86页

作者： Lin Ma Lingqiao Cai Qiaomei Jin Jiajia Liang Dongjian Zhang Wei Liu Yicheng Ni Zhiqi Yin Jian Zhang Ke Pan Department of Natural Medicinal Chemistry & Department of TCMs Pharmaceuticals School of Traditional Chinese Pharmacy China Pharmaceutical University Affliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine Laboratories of Translational Medicine Jiangsu Province Academy of Traditional Chinese Medicine College of Pharmacy Nanjing University of Chinese Medicine Department of Nuclear Medicine The First Affiliated Hospital of Nanjing Medical University Theragnostic Laboratory Campus Gasthuisberg

This study aimed to seek necrosis avid agents with high safety from DNA binding agents. The interaction of 5-hydroxytryptophan(5-HTP) with DNA was investigated by a series of spectroscopic studies. Then, 5-HTP was labeled with iodine-131([^(131)I]5-HTP) and the necrosis avidity of [^(131)I]5-HTP was evaluated by in vitro cell binding assays, in vivo biodistribution experiments and blocking experiment. Finally, the potential of [^(131)I]5-HTP to image necrotic myocardium was explored in rat models with myocardial infarction by SPECT/CT imaging. Results showed that 5-HTP bound to DNA in groove binding mode and the binding constant was 1.69×10~4 L/mol. [~(^(131))I]5-HTP showed specific affinity to necrotic A549 cells,which might be related to cell nucleus. Biodistribution and autoradiography results showed preferential accumulation of [^(131)I]5-HTP in necrotic muscle(necrotic/viable muscle ratio: 6.95 ? 0.68 at 3 h postinjection(p.i.)), which could be blocked by 5-HTP with 66.7% decline, indicating that [^(131)I]5-HTP might share the same necrotic targets with 5-HTP. On SPECT/CT images, a hotspot was clearly observed at 3h *** the necrotic myocardium while not in the control myocardium. In conclusion, [^(131) I]5-HTP is a novel necrosis avid agent and can rapidly visualize necrotic myocardium at 3 h p.i. The necrosis avidity mechanism of [^(131) I]5-HTP may be attributed to its interactions with exposed DNA in the necrotic tissues.

关键词： Radioiodinated 5-hydroxytryptophan Necrosis avidity DNA Groove binding necrotic myocardium imaging

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REGENERATION OF RE-COVERED BARK IN EUCOMMIA ULMOIDES

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Science China Chemistry 1983年第1期26卷 33-40页

作者：李正理崔克明袁正道刘世进 Beijing Qingdao Department of Biology Peking Uniuersity Purchasing Station of Medicinal Plants

The girdled trunk of Eucommia ulmoidcs, sometimes could not regenerate a new bark due to ringed surface necrosis. But, if an extension of 10cm of the bark on each end of the necrotic part was removed in time and re-covered with new bark taken from another tree, the re-covered bark and the newly girdled part could heal together one week after. Opposite to the necrotic surface the loose part of the re-covered bark regenerated callus from the phloem ray cells. If the te-covered part was very close to the necrotic surface, no callus was regenerated. However. many scattered tracheid-like elements derived from phloem were found. And then groups of cells including several tracheid-like elements were discernible. There was a ring of meristematic cells around that group of cells. Finally these meristems gradually became normal and had usual activities of vascular cambium.

关键词： necrotic covered trunk Eucommia regenerated sometimes loose differentiated immature usual

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CLINICAL OBSERVATION ON THERAPEUTIC EFFECTS OF GUZHIZAISHENG WAN FOR TREATMENT OF ASEPTIC NECROSIS OF THE HEAD OF FEMUR

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Journal of Traditional Chinese Medicine 1997年第2期17卷 127-129页

作者：王璐琳 Dong Ya Institute of Osteopathy East District Beijing 100015

Aseptic necrosis of the head of femur falls into the category of "Gushi" (corroded bone) in traditional Chinese medicine (TCM). Its pathogenesis is due to pathogenic factors invading channels,

关键词： invading pathogenesis femur pathogenic necrotic femoral category medial severity Radix

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Effects of Lactobacillus acidophilus on the growth performance and intestinal health of broilers challenged with Clostridium perfringens

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Journal of Animal Science and Biotechnology 2018年第3期9卷 689-698页

作者： Zhui Li Weiwei Wang Dan Liu Yuming Guo State Key Laboratory of Animal Nutrition College of Animal Science and Technology China Agricultural University

Background: Clostridium perfringens is the main etiological agent of necrotic enteritis. Lactobacil i show beneficial effects on intestinal health in infectious disease, but the protective functions of lactobacil i in C. perfringens-infected chickens are scarcely described. This study examined the effects of Lactobacil us acidophilus(L. acidophilus) on the growth performance and intestinal health of broiler chickens chal enged with Clostridium perfringens(C. perfringens) over a 28-day period. Using a 2 × 2 factorial arrangement of treatments, a total of 308 1-day-old male Arbor Acres broiler chicks were included to investigate the effects of Lactobacil us acidophilus(L. acidophilus) on the growth performance and intestinal health of broiler chickens chal enged with Clostridium perfringens(C. perfringens) during a 28-day ***: During infection(d 14–21), C. perfringens challenge decreased the average daily gain(P < 0.05), and increased feed conversion ratio and the mortality rate(P < 0.05). However, dietary supplementation with L. acidophilus increased the body weight of C. perfringens-infected broilers on d 21(P < 0.05), and tended to decrease the mortality(P = 0.061).C. perfringens challenge decreased the villus height(P < 0.05), the ratio of villus height to crypt depth(P < 0.05) and OCLN(occludin) m RNA expression(P < 0.05), and increased the pro-inflammatory cytokine expression in the spleen and jejunum, the intestinal populations of C. perfringens and Escherichia(P < 0.05), and the serum content of endotoxin(P < 0.05), regardless of L. acidophilus supplementation. In contrast, dietary L. acidophilus reducedthe intestinal lesion score of challenged broilers(P < 0.05), the m RNA expression of pro-inflammatory cytokines, ileal populations of Escherichia and serum endotoxin content(P < 0.05), but increased the intestinal Lactobacillus populations(P < 0.05),irrespective of C. perfringens ***: Dietary addition of L. acidophilus could improve

关键词： Broiler Clostridium perfringens Intestine Lactobacillus acidophilus necrotic enteritis

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Bioengineering Functional Copolymers. XVII. Interaction of Organoboron Amide-Ester Branched Derivatives of Poly(Acrylic Acid) with Cancer Cells

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Journal of Cancer Therapy 2011年第2期2卷 266-275页

作者： Mustafa Türk Gülten Kahraman Sevda A. Khalilova Zakir M. O. Rzayev Serpil Oguztüzün Institute of Science & Engineering Division of Nanoscience and Nanomedicine Hacettepe University Ankara Turkey.

Novel bioengineering functional organoboron polymers were synthesized by 1) amidolysis of poly(acrcylic acid) (PAA) with 2-aminoethyldiphenyl borinate (2-AEPB), 2) esterification of organoboron PAA polymer (PAA-B) with a-hydroxy-methoxypoly(ethylene oxide) (PEO) as a compatibilizer and 3) conjugation of organoboron PEO branches (PAA-B-PEO) with folic acid (FA) as a targeting agent. Structure and composition of the synthesized polymers were characterized by FTIR-ATR and 1H (13C) NMR spectroscopy, chemical and physical analysis methods. Anti-tumor activity of organoboron functional polymer and its complex with FA (PAA-B-PEO-F) against cancer and normal cells were evaluated by using different biochemical methods such as cytotoxicity, statistical, apoptotic and necrotic cell indexes, double staining and caspase-3 immune staining, light and fluorescence inverted microscope analyses. It was found that citotoxicity and apoptotic/necrotic effects of polymers significantly depend on the structure and composition of studied polymers, and increase the following raw: PAA << PAA-B < PAA-B-PEO < PAA-B-PEO-F. Among them, PAA-B-PEO-F complex at 400 mg mL–1 concentration as a therapeutic drug exhibits minimal toxicity toward the nor-mal cells, but influential for HeLa cancer cells.

关键词： Synthesis Amidolysis Organoboron Polymers Conjugation Citotoxicity Apoptotic and necrotic Effects

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A Disruptive Treatment to Prevent Amputation and Enhance Limb Salvage in an Elderly Patient

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Journal of Cosmetics, Dermatological Sciences and Applications 2019年第2期9卷 129-154页

作者： Sarah Cristina Castillo Benitez Rosa Alduey Duran Pilar Matos-Ruiz Madalene C. Y. Heng Thomas L. Vander Laan Department of Medicine/Dermatology UCLA School of Medicine Los Angeles USA

Background: Chronic wounds are a growing problem internationally, termed a silent epidemic. To combat this epidemic, it is not sufficient to rely on traditional wound care treatments alone, but to look to innovative and alternative therapies. The indispensable role of oxygen in wound healing is well-discussed in the literature, and in the past two decades the topical application of oxygen has shown promising results in the healing of chronic wounds. However, the toxic effects of oxygen are usually not appreciated and can often lead to wound necrosis and gangrene in wounds with compromised blood supply. While wounds with adequate blood supply contain free radical quenchers (catalase, superoxide dismutase and reduced glutathione) which neutralize the free radicals (reactive oxygen species) released as a by-product of the Krebs cycle, wounds with deficient blood supply are deficient in free radical quenchers and are further damaged by exposure to oxygen as a result of reperfusion injury/oxygen toxicity. Topical hyperbaric oxygen (THOT®) uses low oxygen tensions in the hyperbaric range to stimulate angiogenesis, while preventing excessive oxygen toxicity. The result is the induction of marked angiogenesis, with increasing capacity for quenching reactive oxygen species, resulting in wound healing of ischemic wounds. Case Presentation: This case report describes a 95-year-old Caucasian female who presented with a stage IV chronic necrotic ulcer on her lower left leg. Surgical pathology results revealed calcifying vasculopathy, which is thought to be responsible for deficient blood supply to the leg, leading to a necrotic, chronic leg ulcer of her left leg. After traditional wound therapies were unsuccessful, she was considered for leg amputation. The introduction of adjunctive treatment with topical hyperbaric oxygen therapy saw complete healing of the wound within 15 weeks. The wound remained closed, without the presence of scar tissue, with no signs of wound breakdo

关键词： Limb Salvage necrotic Leg Ulcers Topical Hyperbaric Oxygen Angiogenesis Hypoxic Wounds TcPO2

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On the Principle of Treatment of Burn Wound

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中国烧伤创疡杂志 1993年第2期5卷 41-62页

作者： XU Rongxiang(China National Science and Technology Centre for burns,Wounds and Ulcers Beijing Guangming Chinese Medicine Institute for Burns,Wounds and Ulcers)

The article expounds the therapeutic features of the Moist Exposed Burn Therapy(MEBT)in the treatment of-burn injuries by means of experimental research data and clinical application experiences about MEBT and confirmsthat the principle and method of conventional dry therapy for burn injuries is contrary to burn pathogenesis,whileMEBT is an effective medical technique which is in conformity with burn pathogenesis at *** studies confirmed:microscopical examination of wound tissue treated with dry exposure therapyshowed that the granulation tissue was atrophic,in which the lobocytes exudated,collagenous fibers *** inanimate sign was emerged in the granulation *** wound tissue treated with MEBT wasfull of vitality,fibroblasts proliferated actively and there were aboundant blood *** comparison study be-tween amnion overlying therapy and MEBT in the treatment of superfcialⅢ°burnt wound confrmed that the latercould make the wound heal through epidermization.

关键词： wound atrophic derma pathogenesis injuries necrotic contrary superficial transfusion emerged

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A Great Historical Turn in the Burn Medical Science

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中国烧伤创疡杂志 1989年第1期1卷 62-67页

Whether in war or in *** burns(in-cluding thirmal inluries)*** will natural-ly be led to have resort to the *** is tokeep a burn wound *** method has beenemployed for *** considered both athome and abroad to be the only effective meansso far available Now with his Moist Burn MedicalScience(hereinafter referred to as MBMS)XuRongxiang has challenged such a

关键词： wound treating referred hereinafter necrotic resort peace subcutaneous unable superficial

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